Neurotoxicity of Platinum Compounds: Comparison of the Effects of Cisplatin and Oxaliplatin on the Human Neuroblastoma Cell Line SH-SY5Y

Donzelli, E; Carfì, Maria; Miloso, Mariarosaria; Strada, Alberto; Galbiati, Sara; Bayssas, M.; Griffon-Etienne, Genevieve; Cavaletti, Guido; Petruccioli, M G; Tredici, G

doi:10.1023/b:neon.0000021787.70029.ce

Cited by 68 publications

(52 citation statements)

References 39 publications

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“…Cisplatin was the first platinum-derived drug produced, and is still used as a first-line therapeutic agent against several types of cancers, including NB (36). While the chemotherapeutic effects of cisplatin are based on the formation of an adduct with DNA and proteins, as well as the disruption of several signaling pathways (37,38), the administration of cisplatin is also associated with serious side-effects, including nephrotoxicity and peripheral neuropathy due to immune suppression (39). Due to these toxicities and undesirable side-effects, equally effective and safer treatments are needed.…”

Section: Discussionmentioning

confidence: 99%

Effect of β-carotene on cancer cell stemness and differentiation in SK-N-BE(2)C neuroblastoma cells

Lee

Park²,

Kim³

2013

Oncology Reports

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Abstract. Neuroblastoma is a solid tumor often diagnosed in childhood. While there have been intense efforts to develop a treatment for neuroblastoma, current therapies remain unsuccessful due to high rate of resistance and metastasis. Most cancers originate from a subset of self-renewing cells, primarily cancer stem cells (CSCs), which establish a tumor through continuous self-renewal and differentiation. The successful elimination of CSCs is an important goal in the development of effective strategies to achieve complete remission for cancers. Although β-carotene has been associated with several anticancer mechanisms, the efficacy of β-carotene against CSCs remains unclear. In the present study, β-carotene was shown to reduce cell growth and induce neuronal cell differentiation, concomitant with a marked increase in the phosphorylation of extracellular signal-regulated kinases (ERK) (p42/p44). More importantly, β-carotene inhibited self-renewal characteristics of CSCs and decreased expression of several stem cell markers. Levels of mRNA and protein of Drosophila delta-like 1 homolog (Drosophila) (DLK1) were downregulated following treatment with β-carotene. In addition, knockdown of DLK1 by siRNA enhanced the inhibitory effect of β-carotene on colony formation of neuroblastoma cells. β-carotene also potentiated the effect of cisplatin on the self-renewal characteristics of CSCs in neuroblastoma, revealing that β-carotene has the capacity to resensitize cells to cisplatin cytotoxicity by directly targeting CSCs. In conclusion, β-carotene was shown to strongly increase the anticancer efficacy against neuroblastoma cancer stem-like cells. Moreover, these results suggest that the targeting of CSCs is a novel mechanism of β-carotene. Thus, β-carotene is a potential chemotherapeutic reagent for this cancer.

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Section: Discussionmentioning

confidence: 99%

Effect of β-carotene on cancer cell stemness and differentiation in SK-N-BE(2)C neuroblastoma cells

Lee

Park²,

Kim³

2013

Oncology Reports

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“…The fact that, cisplatin may form with DNA huge adducts, p53-siRNA cannot access the target mRNA sequence, so that p53 expression is still enhanced in cisplatin-treated cells. Recent findings have shown that cisplatin neurocytotoxicity is the result of different apoptosis pathways that involve specific molecules in a complex network (37). However, the diverse role of p73 isoforms in the physiological condition of neuronal cells remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of p73 variants in response to cisplatin treatment in SH-SY5Y neuroblastoma cells

Million

Emilie²,

Goldschneider³

et al. 2006

Int J Oncol

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Abstract. The present study aims to investigate the role of p73 in response to cisplatin treatment in p53 wild-type neuroblastoma SH-SY5Y cells. Results showed that cisplatin induced a dose-dependent up-regulation of p53, p73, and a number of p53-responsive genes. Interestingly, endogenous Δexon2p73-expression was down-regulated by cisplatin treatment. Neither p21 nor GADD45 induction was observed in p53-deficient Lan-1 cells, although endogenous TAp73 expression was markedly induced. In the presence of cisplatin, exogenous TAp73 overexpression in SH-SY5Y cells induced p21 upregulation without altering the apoptotic sub-G1 cell population. Moreover, siRNA-mediated suppression of TAp73 expression did not alter the sub-G1 population. Collectively, our results suggest that wt-p53 SH-SY5Y cells respond to cisplatin by inducing p73 isoform regulation and sustaining p53-dependent apoptosis that is independent of TAp73·. IntroductionNeuroblastoma (NB) is a malignant solid tumor of early childhood which is derived from neural crest precursor cells. Of the antitumor agents used in NB induction chemotherapy, cisplatin is known to exert cytotoxic effects as a result of DNA lesions involving the formation of intra-strand adducts. The resulting inhibition of DNA synthesis is associated with transcription arrest and subsequent cell-cycle inhibitory effects and apoptosis. Unlike most human tumors, NB cells do not exhibit mutated p53 at diagnosis. NB tumors from heavily treated patients can acquire high-level drug resistance during cytotoxic therapy. The subsequent loss of p53 function (1,2) is thought to be possibly due to a series of mutations (3). The p73 protein, which is a structural and functional homologue of the p53 protein, is capable of activating specific target genes and inducing cell-cycle arrest and apoptosis (4,5). Moreover, TPp73 encodes several different isoforms generated by the use of a second promoter or alternative 3'-end splicing (6). The N-terminus of the protein exists in various shorter isoforms that lack a transactivation (TA) domain. The dominant negative inhibitor, ΔNp73·, and the full-length TAp73· are the most studied isoforms to date. Despite the fact that it is located on chromosome 1p36.3, a chromosome which undergoes frequent loss of heterozygosity in some cancers such as NB, the TPp73 gene is rarely mutated in human tumors (7). Recently, it was reported that the TAp73 protein can induce apoptosis through different mechanisms. For that matter, TAp73 in Saos-2 osteosarcoma cells lacking p53 elicits endoplasmic reticulum stress due to the overexpression of scotin, an apoptosis mediator (8). Besides, p73 could activate the death receptors through PUMA transactivation and via Bax mitochondrial translocation (9). Other investigators found that, in the U373MG astroma cell line lacking endogenous p53 (p53 -/p73 + ), TAp73 can sentisize cells to apoptosis through Fas signaling pathway and showed that this apoptosis depends on caspase activation but is not due to variations in deathinducing signaling co...

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“…Although the mode of action of these drugs is to affect the synthesis of nucleic acids and/or proteins, drug resistant cancers have been found. For example, rhabdomyosarcoma was reported to be resistant to platinum-based chemotherapy, where neurotoxicity is the main dose-limiting side effect that prevents higher systemic doses being administered (Donzelli et al, 2004;Jeong et al, 2014). In addition, the extremely rare metastatic spermatocytic seminoma with sarcomatous transformation has been reported to be highly resistant to cytotoxic chemotherapy (Wetherell et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Propolis from the Stingless Bee Trigona incisa from East Kalimantan, Indonesia, Induces In Vitro Cytotoxicity and Apoptosis in Cancer Cell lines

Kustiawan

Phuwapraisirisan²,

Puthong³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: Previously, stingless bee (Trigona spp.) products from East Kalimantan, Indonesia, were successfully screened for in vitro antiproliferative activity against human cancer derived cell lines. It was established that propolis from T. incisa presented the highest in vitro cytotoxicity against the SW620 colon cancer cell line (6% cell survival in 20 µg/mL). In addition, the F45 fraction induced cell cycle arrest at the G1 subphase. Conclusions: Indonesian stingless bee (T. incisa) propolis had moderately potent in vitro anticancer activity on human cancer derived cell lines. Cardol or 5-pentadecyl resorcinol was identified as a major active compound and induced apoptosis in SW620 cells in an early period (≤ 6 h) and cell cycle arrest at the G1 subphase. Thus, cardol is a potential candidate for cancer chemotherapy.

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Neurotoxicity of Platinum Compounds: Comparison of the Effects of Cisplatin and Oxaliplatin on the Human Neuroblastoma Cell Line SH-SY5Y

Cited by 68 publications

References 39 publications

Effect of β-carotene on cancer cell stemness and differentiation in SK-N-BE(2)C neuroblastoma cells

Effect of β-carotene on cancer cell stemness and differentiation in SK-N-BE(2)C neuroblastoma cells

Differential regulation of p73 variants in response to cisplatin treatment in SH-SY5Y neuroblastoma cells

Propolis from the Stingless Bee Trigona incisa from East Kalimantan, Indonesia, Induces In Vitro Cytotoxicity and Apoptosis in Cancer Cell lines

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